Abstract 5251: STAT1 and miR155 expression in human prostate cancer tissue
Authors: Ines Benedetti, Lia Barrios Garcia, Juan Rebollo
Journal: Cancer Research (2019)

Abstract Background: Transcription factors (TFs) and microRNAs (miRNAs) form a gene regulatory network at transcriptional and posttranscriptional level. Increasing evidence shows that miRNAs regulates molecular pathways in cancer by targeting various oncogenes and tumor suppressor genes. However, the mutual regulations between TFs and miRNAs in cancer cells have not been well characterized. Signal transducer and activator of transcription 1 (STAT1) has been reported as a tumor suppressor, but recent evidence suggests that may also play a tumor-promoting role. An STAT1-miR155 feedback loop has been identified in normal tissues. We aimed to explore the STAT1 and miR155 expression in prostate cancer by a bioinformatics analysis combined with immunohistochemical evaluation of STAT1 in normal and prostate cancer tissues. Design: The expression of miR155 was explored in the dbDEMC2 database of Differentially Expressed miRNAs in Human Cancers. Potential targets of this miRNA were searched in the microRNA-target interactions database (miRTarBase), and STAT1 was selected. The protein expression level of STAT1 was analyzed in normal and tumor tissues, from the TCGA databases, by GEPIA bioinformatics tools; and by immunohistochemistry in a prostate tissue microarray (TMA), constructed from prostatectomy samples of patients with localized prostate cancer (PCa), including representative areas from PCa and benign prostate tissue (BPT). Immunohistochemical expression of STAT1 was evaluated by two pathologists, an H-score was obtained for each spot by microscopic assessment of the percentage of epithelial cells with positive staining. Differences in STAT1 expression were assessed by comparing H-Scores between BPT and PCa tissues using Mann-Whitney test, a p value less than 0.05 was considered statistically significant. The Ethical Review Board of the academic institution approved this study. Results: The analysis of miR155 and STAT1 expression in the Genome Cancer Atlas Database showed that both are overexpressed in a variety of tumors including prostate cancer. STAT1 expression at protein level was evaluated in 143 tissue cores representing PCa, and 78 tissue cores representing BPT. Mean STAT1 expression in cores with PCa, was significantly higher than mean of STAT1 expression in cores with BPT (p less than 0.0001). There was a higher mean staining score in PCa (210, 95% CI: 196,1-227,8), compared to BPT (105,5, 95% CI: 87,1-123,9). STAT1 staining was present predominantly in the cytoplasm, also in the membrane and nucleus, of prostate cancer tumor cells. Conclusions: Although miR155 and STAT1 are supposed to be involved in a negative auto-regulatory feedback mechanism, they were both found overexpressed in most of the prostate cancer tissues, which could be explained by the loss of the regulatory feedback loop equilibrium in the tumor environment. Additional studies to detect the in situ expression of miR155 are in progress to validate these results. Citation Format: Ines Benedetti, Lia Barrios Garcia, Juan Rebollo. STAT1 and miR155 expression in human prostate cancer tissue [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 5251.